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| ID | Type | Description | Link |
|---|---|---|---|
| IRB- 2016P000079 | Other Identifier | Beth Israel Deaconess Medical Center |
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| Name | Class |
|---|---|
| Beth Israel Deaconess Medical Center | OTHER |
| Brigham and Women's Hospital | OTHER |
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Processed carbohydrates cause rapid changes in blood sugar and have been associated with overeating and obesity. We have shown that test meals high in processed carbohydrate affect brain areas involved in addiction, craving and overeating. It is unknown whether the changes in blood sugar or the associated higher insulin levels mediate this brain activation and its likely adverse effects.
Answering this question is important for patients with type 1 diabetes who have elevated risks of obesity and disordered eating: If blood sugar is the causal mechanism, optimal insulin coverage should be protective. If insulin is the causal mechanism, however, a diet high in processed carbohydrate could predispose to overeating and weight gain, as this diet requires higher insulin doses.
To disentangle these factors, we will study brain activation and relevant blood markers in 15 men with diabetes. In 4 sessions, we will examine meals with differential carbohydrate properties while giving insulin infusions.
A total of 15 male participants (age 18-45) with T1DM will be recruited. Participants will be enrolled in the study for a total of 1-3 months, and participate in a pre-test visit and three test visits, each after a 10-12-hr overnight fast. Participants will be instructed to consume their regular, weight maintaining diet between visits.
At the pre-test visit, the study director or PI will meet participants, confirm eligibility and obtain informed consent. Participants will receive a low glycemic index (GI) meal with optimal iv insulin coverage using a negative feedback algorithm to maintain euglycemia (euglycemic clamp). Insulin requirement will be quantified. At some time during the visit, participants will present to the BIDMC research imaging facility for a practice MRI session, during which they will undergo a brief imaging sequence to get accustomed to the scanning process and eliminate anxiety as a confounder of imaging data.
At each of 3 test visits, one of the following experimental conditions will be applied in a randomized, blinded cross-over design: (a) high GI meal with euglycemic clamp, (b) low GI meal with euglycemic clamp, (c) high GI meal with primed-variable insulin infusion at the rate established during the pre-test visit. After steady state is established, baseline laboratory evaluation and MRI imaging will be obtained, followed by the test meal. Imaging will be repeated at 1 and 4 hours postprandial. Blood samples for pertinent metabolic and hormonal parameters will be obtained every 30 minutes. Each test-visit concludes with a standard weighed meal to quantify ad-libitum intake.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| high GI meal, euglycemic insulin clamp | Experimental | A nutritional shake with high GI will be consumed. Regular insulin will be administered intravenously according to a negative feedback algorithm to maintain euglycemia.This condition results in euglycemia with high insulin levels. |
|
| high GI meal, fixed insulin infusion | Experimental | A nutritional shake with high GI will be consumed. Regular insulin will be administered intravenously at a rate previously established to maintain euglycemia after a low glycemic index meal. This condition results in moderate hyperglycemia with low insulin levels. |
|
| low GI meal, euglycemic insulin clamp | Active Comparator | A nutritional shake with low GI will be consumed. Regular insulin will be administered intravenously according to a negative feedback algorithm to maintain euglycemia. This condition results in euglycemia with low insulin levels. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| high GI meal | Other | High and low GI liquid test meals are matched for macronutrient composition (60% carbohydrate, 15% protein, 25% fat), micronutrient profiles, physical properties, palatability and sweetness. Meals will provide 25% of individual daily energy requirements as estimated by the Harris Benedict equation. A high glycemic index of ~90 is achieved by using corn syrup as a carbohydrate source. |
| Measure | Description | Time Frame |
|---|---|---|
| Nucleus Accumbens Blood Flow | Cerebral blood flow in the right and left nucleus accumbent was measured by arterial spin labeling (MRI). Blood flow was normalized for whole brain perfusion and corrected for baseline perfusion in the respective brain area and meal order, as per our a priori statistical analysis plan. | 4 hrs postprandial |
| Measure | Description | Time Frame |
|---|---|---|
| Nucleus Accumbens Blood Flow | Cerebral blood flow in the right and left nucleus accumbent was measured by arterial spin labeling (MRI). Blood flow was normalized for whole brain perfusion and corrected for baseline perfusion in the respective brain area and meal order, as per our a priori statistical analysis plan. | 1 hr postprandial |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Glucose Level | blood samples will be obtained every 30 minutes | 0-4.5 hrs postprandial |
| Serum Insulin Level | blood samples will be obtained every 30 minutes |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Belinda S Lennerz, MD, PhD | Boston Children's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02115 | United States |
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Participants underwent a 5 hour pre-randomization visit to establish IV insulin requirement for a low GI test meal. Participants were positioned in the MRI scanner for a brief test sequence.
Participants were excluded if they were unable to finish these pre-randomization procedures, or if they decided to not continue.
Participants were recruited from the Boston Children's Hospital Diabetes Program and via postings in the surrounding medical area.
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| ID | Title | Description |
|---|---|---|
| FG000 | High GI Matched Glucose - Low GI - High GI Matched Insulin | In a randomized cross-over design, a nutritional shake with high GI vs low GI was consumed with differential insulin coverage in the following order:
High and low GI liquid test meals were matched for macronutrient composition (60% carbohydrate, 15% protein, 25% fat), micronutrient profiles, physical properties, palatability and sweetness. Meals provided 25% of individual daily energy requirements. Insulin was given intravenously for 5 hours. Glucose levels were measured every 5 minutes for insulin titration. |
| FG001 | High GI Matched Insulin - Low GI - High GI Matched Glucose | In a randomized cross-over design, a nutritional shake with high GI vs low GI was consumed with differential insulin coverage in the following order:
High and low GI liquid test meals were matched for macronutrient composition (60% carbohydrate, 15% protein, 25% fat), micronutrient profiles, physical properties, palatability and sweetness. Meals provided 25% of individual daily energy requirements. Insulin was given intravenously for 5 hours. Glucose levels were measured every 5 minutes for insulin titration. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Experimental Condition 1, 1 Day |
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| Wash-out, 1 Week |
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| Comparison Condition, 1 Day |
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| Wash-out, 1 Week |
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| Experimental Condition 2, 1 Day |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | In a randomized cross-over design, a nutritional shake with high GI vs low GI was consumed with differential insulin coverage:
The order of experimental conditions A and B was randomized. High and low GI liquid test meals were matched for macronutrient composition (60% carbohydrate, 15% protein, 25% fat), micronutrient profiles, physical properties, palatability and sweetness. Meals provided 25% of individual daily energy requirements. Insulin was given intravenously for 5 hours. Glucose levels were measured every 5 minutes for insulin titration. Because all participants completed all interventions, results are presented in aggregate for the entire study group. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Nucleus Accumbens Blood Flow | Cerebral blood flow in the right and left nucleus accumbent was measured by arterial spin labeling (MRI). Blood flow was normalized for whole brain perfusion and corrected for baseline perfusion in the respective brain area and meal order, as per our a priori statistical analysis plan. | Posted | Least Squares Mean | Standard Error | ml/g/min per ml/g/min | 4 hrs postprandial |
|
Enrollment through study completion (on average 2 months).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | High GI With Matched to Low GI Glucose (HGI HI) | After an overnight fast, a nutritional shake with high GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes, and Insulin was adjusted using a negative feedback algorithm to maintain euglycemia. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tachycardia | Cardiac disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Belinda Lennerz | Boston Children's Hospital | 617 355 7476 | belinda.lennerz@childrens.harvard.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 26, 2016 | Mar 25, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D050177 | Overweight |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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|
| low GI meal | Other | High and low GI liquid test meals are matched for macronutrient composition (60% carbohydrate, 15% protein, 25% fat), micronutrient profiles, physical properties, palatability and sweetness. Meals will provide 25% of individual daily energy requirements as estimated by the Harris Benedict equation. A low glycemic index of ~40 is achieved by using uncooked corn starch as a carbohydrate source. |
|
| euglycemic insulin clamp | Drug | Insulin will be given intravenously for 5 hours. During the entire clamp protocol, glucose levels will be measured every 5 minutes. A basal insulin infusion will be started at 80% of the patients insulin pump basal rate, and will be adjusted between 0.1 and 2.5 mU/kg•min, depending upon the patient's plasma glucose level in relation to the target range target of 90-100 mg/dl. |
|
| primed-variable insulin infusion | Drug | A primed-variable infusion of insulin will be administered at the rate established to achieve euglycemia after a low glycemic index meal. This is expected to result in moderate hyperglycemia as the high GI meal is associated with higher insulin requirements. For patient safety, glucose levels will be measured every 30 minutes. If glucose levels are > 400 mg/dl or < 60 mg/dl, insulin infusion will be adjusted to maintain glucose levels target of 60-400 mg/dl. |
|
| Blood Flow in Other Brain Areas Involved in Intake Regulation - Dorsal Caudate |
Cerebral blood flow was measured by arterial spin labeling (MRI). Grouped MRI data was visually inspected for postprandial differences between conditions. Blood flow from a cluster contracting the conditions in the right dorsal caudate, just lateral to the nucleus accumbent, was extracted, normalized for whole brain perfusion and corrected for baseline perfusion in the respective brain area and meal order, as per our a priori statistical analysis plan. |
| 4 hrs postprandial |
| Blood Flow in Other Brain Areas Involved in Intake Regulation - Ventrolateral Striatum | Cerebral blood flow was measured by arterial spin labeling (MRI). Grouped MRI data was visually inspected for postprandial differences between conditions. Blood flow from a cluster contracting the conditions in the right ventrolateral striatum, just lateral to the nucleus accumbent, was extracted, normalized for whole brain perfusion and corrected for baseline perfusion in the respective brain area and meal order, as per our a priori statistical analysis plan. | 1 hr postprandial |
| Functional Connectivity of Nucleus Accumbens, Hypothalamus and Other Brain Areas Involved in Intake Regulation | Cerebral blood oxygen concentration level was measured by resting state functional MRI (rs-fMRI). Seed based analysis was performed with the seed on the right Nucleus Accumbens. Functional connectivity between Nucleus Accumbens and Hypothalamus was assessed through extraction of temporal correlation measures. | 4 hrs postprandial |
| Functional Connectivity of Nucleus Accumbens, Hypothalamus and Other Brain Areas Involved in Intake Regulation | Cerebral blood oxygen concentration level was measured by resting state functional MRI (rs-fMRI). Seed based analysis was performed with the seed on the right Nucleus Accumbens. Functional connectivity between Nucleus Accumbens and Hypothalamus was assessed through extraction of temporal correlation measures. Functional connectivity between Nucleus Accumbens and other brain areas was visually assessed. | 1 hr postprandial |
| 0-4.5 hrs postprandial |
| Serum Fatty Acids | blood samples will be obtained every 30 minutes | 0-4.5 hrs postprandial |
| Plasma Ghrelin | blood samples will be obtained every 30 minutes and analyzed as part of a metabolic hormone panel | 0-4.5 hrs postprandial |
| Plasma GLP-1 | blood samples will be obtained every 30 minutes and analyzed as part of a metabolic hormone panel | 0-4.5 hrs postprandial |
| Plasma PYY | blood samples will be obtained every 30 minutes and analyzed as part of a metabolic hormone panel | 0-4.5 hrs postprandial |
| Plasma CCK | analyzed as part of a metabolic hormone panel | 0-4.5 hrs postprandial |
| Plasma Glucagon | blood samples will be obtained every 30 minutes and analyzed as part of a metabolic hormone panel | 0-4.5 hrs postprandial |
| Plasma Leptin | analyzed as part of a metabolic hormone panel | 0-4.5 hrs postprandial |
| Metabolomics | LC-MS/MS methodology using several chromatographic stationary phases for > 400 metabolites | 0, 1 and 4 hrs postprandial |
| NOT COMPLETED |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| BMI | Mean | Standard Deviation | kg/m^2 |
|
| OG001 | Low GI (LGI) | After an overnight fast, a nutritional shake with low GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes, and Insulin was adjusted using a negative feedback algorithm to maintain euglycemia. Interventions were presented in a cross-over design. Because all participants completed all interventions, results are presented by intervention. |
| OG002 | High GI With Matched to Low GI Insulin (HGI LI) | After an overnight fast, a nutritional shake with high GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes. Insulin was given at the same rates as determined appropriate for each participant during the pre-randomization visit or the LGI visit. Interventions were presented in a cross-over design. Because all participants completed all interventions, results are presented by intervention. |
|
|
| Secondary | Nucleus Accumbens Blood Flow | Cerebral blood flow in the right and left nucleus accumbent was measured by arterial spin labeling (MRI). Blood flow was normalized for whole brain perfusion and corrected for baseline perfusion in the respective brain area and meal order, as per our a priori statistical analysis plan. | Posted | Least Squares Mean | Standard Error | ml/g/min per ml/g/min | 1 hr postprandial |
|
|
|
| Secondary | Blood Flow in Other Brain Areas Involved in Intake Regulation - Dorsal Caudate | Cerebral blood flow was measured by arterial spin labeling (MRI). Grouped MRI data was visually inspected for postprandial differences between conditions. Blood flow from a cluster contracting the conditions in the right dorsal caudate, just lateral to the nucleus accumbent, was extracted, normalized for whole brain perfusion and corrected for baseline perfusion in the respective brain area and meal order, as per our a priori statistical analysis plan. | Posted | Least Squares Mean | Standard Error | ml/g/min per ml/g/min | 4 hrs postprandial |
|
|
|
| Secondary | Blood Flow in Other Brain Areas Involved in Intake Regulation - Ventrolateral Striatum | Cerebral blood flow was measured by arterial spin labeling (MRI). Grouped MRI data was visually inspected for postprandial differences between conditions. Blood flow from a cluster contracting the conditions in the right ventrolateral striatum, just lateral to the nucleus accumbent, was extracted, normalized for whole brain perfusion and corrected for baseline perfusion in the respective brain area and meal order, as per our a priori statistical analysis plan. | Posted | Least Squares Mean | Standard Error | ml/g/min per ml/g/min | 1 hr postprandial |
|
|
|
| Secondary | Functional Connectivity of Nucleus Accumbens, Hypothalamus and Other Brain Areas Involved in Intake Regulation | Cerebral blood oxygen concentration level was measured by resting state functional MRI (rs-fMRI). Seed based analysis was performed with the seed on the right Nucleus Accumbens. Functional connectivity between Nucleus Accumbens and Hypothalamus was assessed through extraction of temporal correlation measures. | Posted | Least Squares Mean | Standard Error | unite-less correlation | 4 hrs postprandial |
|
|
|
| Secondary | Functional Connectivity of Nucleus Accumbens, Hypothalamus and Other Brain Areas Involved in Intake Regulation | Cerebral blood oxygen concentration level was measured by resting state functional MRI (rs-fMRI). Seed based analysis was performed with the seed on the right Nucleus Accumbens. Functional connectivity between Nucleus Accumbens and Hypothalamus was assessed through extraction of temporal correlation measures. Functional connectivity between Nucleus Accumbens and other brain areas was visually assessed. | Posted | Least Squares Mean | Standard Error | unite-less correlation | 1 hr postprandial |
|
|
|
| Other Pre-specified | Plasma Glucose Level | blood samples will be obtained every 30 minutes | Not Posted | 0-4.5 hrs postprandial | Participants |
| Other Pre-specified | Serum Insulin Level | blood samples will be obtained every 30 minutes | Not Posted | 0-4.5 hrs postprandial | Participants |
| Other Pre-specified | Serum Fatty Acids | blood samples will be obtained every 30 minutes | Not Posted | 0-4.5 hrs postprandial | Participants |
| Other Pre-specified | Plasma Ghrelin | blood samples will be obtained every 30 minutes and analyzed as part of a metabolic hormone panel | Not Posted | 0-4.5 hrs postprandial | Participants |
| Other Pre-specified | Plasma GLP-1 | blood samples will be obtained every 30 minutes and analyzed as part of a metabolic hormone panel | Not Posted | 0-4.5 hrs postprandial | Participants |
| Other Pre-specified | Plasma PYY | blood samples will be obtained every 30 minutes and analyzed as part of a metabolic hormone panel | Not Posted | 0-4.5 hrs postprandial | Participants |
| Other Pre-specified | Plasma CCK | analyzed as part of a metabolic hormone panel | Not Posted | 0-4.5 hrs postprandial | Participants |
| Other Pre-specified | Plasma Glucagon | blood samples will be obtained every 30 minutes and analyzed as part of a metabolic hormone panel | Not Posted | 0-4.5 hrs postprandial | Participants |
| Other Pre-specified | Plasma Leptin | analyzed as part of a metabolic hormone panel | Not Posted | 0-4.5 hrs postprandial | Participants |
| Other Pre-specified | Metabolomics | LC-MS/MS methodology using several chromatographic stationary phases for > 400 metabolites | Not Posted | 0, 1 and 4 hrs postprandial | Participants |
| 0 |
| 15 |
| 0 |
| 15 |
| 1 |
| 15 |
| EG001 | Low GI (LGI) | After an overnight fast, a nutritional shake with low GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes, and Insulin was adjusted using a negative feedback algorithm to maintain euglycemia. | 0 | 15 | 0 | 15 | 0 | 15 |
| EG002 | High GI With Matched to Low GI Insulin (HGI LI) | After an overnight fast, a nutritional shake with high GI was consumed. The shake provided 25% of daily calorie requirements with a macronutrient composition of 60% carbohydrate, 15% protein, 25% fat, and matched micronutrient profiles, physical properties, palatability and sweetness. Insulin was given intravenously to normalize blood glucose before the meal and for 5 hours postprandial. Blood glucose levels were measured every 5 minutes. Insulin was given at the same rates as determined appropriate for each participant during the pre-randomization visit or the LGI visit. | 0 | 15 | 0 | 15 | 1 | 15 |
| dizzyness | Cardiac disorders | Systematic Assessment |
|
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| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
|